Nanoparticle complexes of paclitaxel, trastuzumab, and albumin

Abstract

Described are stable nanoparticle complexes of 100 nm to 900 nm comprising paclitaxel, albumin and an antibody. The nanoparticle complexes are suitable for the treatment of cancer.

What is claimed is: 
     
       1. An antibody-albumin nanoparticle complex comprising albumin, a trastuzumab antibody, and a therapeutically effective amount of paclitaxel, wherein the nanoparticle complex has been pre-formed in vitro by mixing an aqueous albumin-paclitaxel nanoparticle with the antibody under conditions to form the nanoparticle complex, such that the antibody portion of said complex retains HER2 binding specificity, wherein the complex has a diameter of between 0.1 μm and 1 μm. 
     
     
       2. The antibody-albumin nanoparticle complex of  claim 1 , said complex having a diameter between 0.1 μm and 0.9 μm. 
     
     
       3. The antibody-albumin nanoparticle complex of  claim 1 , said complex having a diameter of between 0.1 μm and 0.3 μm. 
     
     
       4. The antibody-albumin nanoparticle complex of  claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 5:1 and 1:2.5. 
     
     
       5. The antibody-albumin nanoparticle complex of  claim 1 , wherein said nanoparticle complex comprises an alkylating agent. 
     
     
       6. The antibody-albumin nanoparticle complex of  claim 5 , wherein said alkylating agent is a platinum compound. 
     
     
       7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of antibody-albumin nanoparticle complexes, said nanoparticle complexes comprising albumin, a trastuzumab antibody, and a therapeutically effective amount of paclitaxel, wherein the nanoparticle complexes have been pre-formed in vitro by mixing aqueous albumin-paclitaxel nanoparticles with the antibody under conditions to form the nanoparticle complexes, such that the antibody retains HER2 binding specificity, wherein the average diameter of at least 90 percent of said complexes is between 0.1 μm and 1 μm. 
     
     
       8. The pharmaceutical composition of  claim 7 , wherein the average diameter of at least 90 percent of said complexes is between 0.1 μm and 0.9 μm. 
     
     
       9. The pharmaceutical composition of  claim 7 , wherein the average diameter of said complexes is between 0.1 μm and 0.3 μm. 
     
     
       10. The pharmaceutical composition of  claim 7 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 5:1 and 1:2.5. 
     
     
       11. The pharmaceutical composition of  claim 7 , wherein said composition comprises an alkylating agent. 
     
     
       12. The pharmaceutical composition of  claim 11 , wherein said alkylating agent is a platinum compound. 
     
     
       13. The pharmaceutical composition of  claim 7  which is formulated for injection. 
     
     
       14. The pharmaceutical composition of  claim 7 , wherein the pharmaceutically acceptable carrier is saline, water, lactic acid, mannitol, or a combination thereof.